Current Drug Therapy (v.4, #2)

Utilization of Traditional Antimalarial Ethnophytotherapeutic Remedies Among Assendabo Inhabitants in (South-West) Ethiopia by Sultan Suleman, Zeleke Mekonnen, Gizachew Tilahun, Shyama Chatterjee (78-91).
Background: Plants in Ethiopia have become increasingly important as sources of traditional medicines. The World Health Organization (WHO) estimates that malaria kills 2.7 million people every year, 90and#x25; of who are from Africa. Malaria continues to be a national concern in Ethiopia as it plays a major role in the high mortality rates being experienced currently. The country has witnessed recurrent epidemics of the disease with grave consequences. The use and misuse of chloroquine to prevent and treat falciparum malaria have led to widespread appearance of chloroquine resistant parasites in Ethiopia and other tropical countries. These factors and the rising costs of non-chloroquine drugs have made the local people turn to traditional remedies for malaria management. This paper examines the current utilization of traditional plant medicines in managing malaria among the inhabitants of Assendabo Township in Jimma, Ethiopia. Method: A cross-sectional study was done on randomly selected inhabitants of Assendabo town and surrounding villages, using structured pre-tested questionnaires. Results: Both indigenous and introduced species of plants were in use, indicating that traditional medicinal practices in this region are dynamic. In total 8 species in 13 plant types were identified. The most common species used were and#x2018;Armagusaand#x2019; Ajuga remota and and#x2018;Birbira or Hallekoand#x2019; Moringa olifera. The Ajuga species was a common ingredient in almost all medications used, while both these species reported anti-malarial effectivity. In most cases the plant extracts to be used for medication were obtained in a destructive manner, requiring conservation measures to ensure sustainable utilization. Conclusions: This study reiterates that a considerable proportion of the Ethiopian community uses traditional medicine to treat malaria and other diseases. The results of this study become a basis for selecting plants for further pharmacological and phytochemical studies to develop new and locally relevant anti-malarial agents in Ethiopia.

Ethosomes and its Applications in Transdermal Drug Delivery by Rajashree Hirlekar, Harshal Garse, Suneeta Sonawane, Sujata Londhe, Vilasrao Kadam (92-100).
Nanotechnology, for the past few years, has evolved as a new era of drug delivery for many drug systems. Transdermal drug delivery is one of the few systems which have been a major area of research these days. Transdermal Drug Delivery System (TDDS) offers many advantages as compared to traditional drug delivery systems. However TDDS has limited market success due to the barrier properties of the Stratum Corneum. Introduction of ethosomes, which are soft, malleable vesicular carriers containing ethanol tailored for enhanced delivery of active agents, has initiated a new area on vesicular research for transdermal drug delivery. Different reports show a promising future of ethosomes in making transdermal delivery of various agents more effective. Ethosomes also offer a good opportunity for the non-invasive delivery of small, medium, and large sized drug molecules. Preparation of ethosomes is easy with no complicated equipment involved and therefore can be scaled up to industrial level. This review includes introduction to ethosomes, composition and methods of preparation, evaluation and effectiveness in skin permeation. The review also highlights use of ethosomes in transdermal drug delivery in terms of quantity and depth than either liposomes or hydroalcoholic solutions.

The clinical use of Botulinum toxin (BoTx) in motor paralytic disorders until now is limited to spasticity relief in isolated spastic muscle/s. This paper advocates that BoTx should be used as a neuro-relearning tool that can significantly improve recovery in motor paralytic disorders. BoTx generates redundant numbers of synapses at motor endplates and at spinal motoneuron-interneurons. It facilitates muscle activity-dependent synapse competition at these two sites. Redundancy and competition-based selection of synaptic connections are naturally occurring learning- related plasticity events during infant motor learning- now familiarly known as competitive-learning. Thus when injected in small doses to multiple muscles of a paralyzed limb, BoTx can recreate and replay those competitive-learning processes in the learningresistant paralyzed brain centers. Computational modeling, humanoid robot, and animal studies reveal that motor re) learning can be significantly faster if competitive-learning mechanisms are employed in the paralyzed system. A treatment protocol is presented that aims to keep the paralyzing effects of BoTx minimized while prolonging relearning duration. Recent clinical studies strongly attest that small-dose; multi-muscle, repeat regimens improve function. The principal objective of the present paper is that future multi-muscle clinical studies will take note of the relearning properties of BoTx and make full utilization of this therapeutic effect.

Comparative In Vitro Antimicrobial Activity of Pantoprazole, Tetracycline and a Fixed Dose Combination in Helicobacter pylori Infection by Dharmendra Rai, Vivek Dwivedi, Manu Chaudhary, Sanjay Shrivastava, Praveen Rishi, Pramod Pandey (106-110).
Fixed dose combinations of Pantoprazole and Tetracycline (PT) have a wider range of susceptibility than any one of these two drugs individually. The present study was carried out to determine the Minimum Inhibitory Concentration (MIC) and Time kill curve of Pantoprazole, Tetracycline and a fixed dose combination of these two drugs in four groups (HP-B1, HP-B2, HP-B3, HP-B4) of Helicobacter pylori (H. pylori) bacteria. The MIC were found to be 0.03125 mg/l, 0.03125 mg/l, 0.03125 mg/l, and 0.0625 mg/l for PT, 32mg/l, 64mg/l, 32mg/l, 64mg/l, respectively, for Pantoprazole and 0.125 mg/l, 0.125mg/l, 0.125mg/l, and 0.25mg/l for tetracycline, respectively, in the different groups . In all H. pylori groups studied, the time-kill curve analysis demonstrated maximum bacterial killing at 4 hours with PT having the most pronounced effect. From the present findings it can be concluded that a fixed dose combination of pantoprazole and tetracycline has better efficacy and more bacterial inhibiting properties than Pantoprazole or Tetracycline alone.

Endocannabinoid Blockade and the Cardiovascular System by Oliver Keown, Ian Megson, Stephen Leslie (111-116).
The endogenous cannabinoid system plays a vital role in appetite, energy homeostasis and the cardiovascular system. Emerging clinical data have shown that selective cannabinoid antagonism of cannabinoid receptors (CB1) using the anti-obesity drug, rimonabant, can reduce cardio-metabolic risk factors in patients. Metabolic improvements observed in several trials are consistent, showing beneficial effects on lipid ratios, glucose control and vascular function, as well as an improvement in other cardio-metabolic biomarkers. Cannabinoid receptors are ubiquitous: the endocannabinoid system is conserved in many organs important to homeostasis control, including the liver, pancreas, skeletal muscle and adipose tissue. The cardiovascular effects of endocannabinoids are mediated through receptors in blood vessels, myocardial cells and platelets, causing changes in vascular tone, heart rate and haemostatic function. Endogenous and exogenous cannabinoids increase platelet aggregation, suggesting that antagonism might have an anti-thrombotic effect. Vasodilator and anti-thrombotic therapies are commonly prescribed to patients with cardiovascular disease, and therefore CB1 receptor antagonists offer great promise as a multi-faceted therapeutic agent. This article reviews the current position reached from cannabinoid studies, with particular reference to the cardiovascular effects of endocannabinoid blockade and the potential future uses of endocannabinoid receptor blockade with drugs such as rimonabant.

Adenoviral Vector-Based Strategies for Cancer Therapy by Anurag Sharma, Manish Tandon, Dinesh Bangari, Suresh Mittal (117-138).
Definitive treatment of cancer has eluded scientists for decades. Current therapeutic modalities like surgery, chemotherapy, radiotherapy and receptor-targeted antibodies have varied degree of success and generally have moderate to severe side effects. Gene therapy is one of the novel and promising approaches for therapeutic intervention of cancer. Viral vectors in general and adenoviral (Ad) vectors in particular are efficient natural gene delivery systems and are one of the obvious choices for cancer gene therapy. Clinical and preclinical findings with a wide variety of approaches like tumor suppressor and suicide gene therapy, oncolysis, immunotherapy, anti-angiogenesis and RNA interference using Ad vectors have been quite promising, but there are still many hurdles to overcome. Shortcomings like increased immunogenicity, prevalence of preexisting anti-Ad immunity in human population and lack of specific targeting limit the clinical usefulness of Ad vectors. In recent years, extensive research efforts have been made to overcome these limitations through a variety of approaches including the use of conditionally-replicating Ad and specific targeting of tumor cells. In this review, we discuss the potential strengths and limitations of Ad vectors for cancer therapy.

Effective Use of Drugs to Counter Chemical Terrorism by Tetsu Okumura, Tomohiro Hitomi, Kenji Hirahara, Takachika Itoh, Takashi Iwamura, Futishi Nagashima, Atsushi Nakashima, Tomokazu Motomura, Ayumi Motomura, Kouichi Ariyoshi, Takako Tominaga, Motohiro Tsuruwa, Kouichiro Suzuki, Kenji Taki (139-143).
In the present international climate, preparedness and effectively responding to chemical terrorism is of serious concern. Given that antidotes are available for chemical agents, such as nerve or blood (cyanide) agents, the key to survival is how quickly and effectively antidotes can be administered in mass casualty events. To counter agents acting on the nervous system, atropine, pralidoxime and diazepam are generally administered, but aside from pralidoxime, no general consensus has been reached regarding the use of oximes, such as obidoxime and HI-6. In addition, the use of diazepam is being investigated in comparison to other benzodiazepines. As antidotes to blood agents, sodium nitrite (or amyl nitrite) and sodium thiosulfate are often used in the United States, but in Europe, dicobalt edetate and hydroxocobalamin are used. In particular, hydroxocobalamin appears to be a promising antidote against blood-agent terrorism. In mass casualty events caused by chemical terrorism, it is also necessary to consider the most effective administration routes of the antidote (intravenous, intramuscular or intraosseous). Hence, it is imperative to adequately discuss when first responders (rescuers) wearing personal protective equipment (PPE) should administer these drugs and who should be in charge of such drug administration. Here these problems are reviewed and discussed with reference to the current literature.

The binding of Beta Adrenoceptor antagonist, propranolol and anti-depressant drug, amitriptyline, to bovine serum albumin (BSA) was studied by equilibrium dialysis (ED) method. During concurrent administration, it was found that amitriptyline has the capacity to release propranolol from its binding site on BSA, causing reduced binding of propranolol to BSA. This increment in free concentration of propranolol was from 5.15and#x25; to 9.15and#x25;, upon the addition of increased concentration of only amitriptyline 0x10-5M to 20x10-5 M, and in the presence of site-II specific probe (diazepam), it was from 6.95and#x25; to 10.45and#x25;. On the other hand, the release of amitriptyline from the binding sites on BSA was increased from 3.08and#x25; to 4.28and#x25; upon the addition of increased concentration of only propranolol 0x10-5 M to 20x10-5 M, and in the presence of site-II specific probe (diazepam), it was 0.51and#x25; to 4.75and#x25;. This form of drug-drug interaction at binding sites on BSA has been termed as site-to-site displacement. Drug-drug interactions, more specifically, displacement interaction will affect the free concentrations drugs in blood. Since the pharmacologic activity of a drug is a function of free drug concentration, the displacement of even a small amount of drug bound to plasma protein could produce considerable increase in activity.

Ceftazidime belongs to cephalosporin class of antibiotics with broad spectrum activity. Tobramycin is an aminoglycoside antibiotic used to treat various types of bacterial infections, particularly gram negative infections. Combination therapy of ceftazidime tobramycin is adopted in many clinical conditions. In present study, the authors have tried to determine the comparative antimicrobial activity of ceftazidime, tobramycin and their novel Fixed Dose Combination (FDC) in some pathogenic microorganisms. Minimum Inhibitory Concentration (MIC) and Antibiotic Susceptibility Test (AST) were performed. The AST results show that the FDC of these antibiotics significantly increased zone of inhibition in all microorganisms as compared to individual therapy of ceftazidime and tobramycin. In case of Morganella morganii and Citrobacter freundii, gram negative bacteria, the antimicrobial activity was increased by 3.69and#x25; and 5.79and#x25; in FDC of these antibiotics when compared tobramycin alone. MIC of FDC of ceftazidime and tobramycin in Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus was much lower in comparison to ceftazidime and tobramycin alone. These results indicate that the FDC of ceftazidime and tobramycin has better bactericidal activity in comparison to ceftazidime and tobramycin alone in organisms under study.